-Waist at age 3 linked to elevated ALT levels by age 8

Higher waist circumference of toddlers predicts development of pediatric nonalcoholic fatty liver disease (NAFLD) by age 8, according to a prospective study.

In a group of young children a median of 3.2-years old, every 10 cm (3.94 in) increase in waist circumference was tied to nearly doubled odds of having elevated alanine aminotransferase (ALT) levels -- a surrogate marker of NAFLD -- by mid-childhood, or around 8 years of age (OR 1.99, 95% CI 1.19 to 3.33).

Greater gain in adiposity from early to mid-childhood was associated with higher odds of elevated ALT at mid-childhood, reported Jennifer Woo Baidal, MD, MPH, of Columbia University Medical Center in New York City, and colleagues online in the Journal of Pediatrics. This relationship was seen across several markers:

BMI z-score (OR 1.58, 95% CI 1.23 to 2.03)

Subscapular/Triceps skinfold (OR 1.53 per 10 mm, 95% CI 1.20 to 1.96)

Waist circumference (OR 1.56 per 10 cm, 95% CI 1.16 to 2.08)

Hip circumference (OR 2.19 per 10 cm, 95% CI 1.53 to 3.13)

Action Points

Note that this longitudinal pediatric study found that adiposity in the early years is associated with elevated ALT levels at around age 8.

Be aware that direct measurement of liver adiposity was not available.

"Some clinicians measure ALT levels in at-risk children starting at around 10 years old, but our findings underscore the importance of acting earlier in a child's life to prevent excess weight gain and subsequent liver inflammation," explained Woo Baidal in a statement. "Currently, the best way for kids and adults to combat fatty liver disease is to lose weight, by eating fewer processed foods and getting regular exercise. We urgently need better ways to screen, diagnose, prevent, and treat this disease starting in childhood."

Although other studies have suggested a link between adiposity and NAFLD, Woo Baidal's group highlighted that this is the first study to show increases in adiposity starting as early as young childhood can negatively effect liver health.

"[I]t is possible that higher waist circumference in early childhood could presage central adiposity and its associated health risks later in life, but the relationship between waist circumference at early childhood and ALT level at mid-childhood has not been previously reported," the group wrote, highlighting the importance of measuring waist circumference in early childhood, despite it not being "uniformly measured as part of routine pediatric clinical care."

The study included 635 children participating in Project Viva who were followed from early childhood to mid-childhood. Clinical data, including height, weight, BMI z-scores, and skinfold testing were conducted at both visits. Blood samples to measure ALT levels were collected at mid-childhood.

Cutoffs for detecting pediatric NAFLD were used as recommended by current guidelines, with SAFETY ALT thresholds at 25.8 U/L for boys and 22.1 U/L for girls among children ages 12 to 17. Based on recent data, however, researchers have argued these cutoffs are too high for reliable detection and should be revised.

Using the even higher CALIPER ALT threshold of 25 U/L for determining NAFLD in both boys and girls, similar yet stronger findings were reported by Woo Baidal's group. In early childhood, every 10 cm increase in waist circumference was tied to more than twice the likelihood of elevated ALT later on (OR 2.37, 1.37 to 4.09). Again, changes in adiposity from early to mid-childhood were associated with an increased risk for NAFLD at age 8.

In a sub-analysis of 527 children from the cohort, the researchers reported other metabolic factors were also predictive of childhood NAFLD, independent of adiposity. In a fully adjusted model, elevated ALT levels were tied to increases of 0.02 units in metabolic risk score, 0.13 mm Hg systolic blood pressure, 0.05 units HOMA-IR, and 0.16 uU/mL fasting insulin.

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